Highly purified biologically active alpha-1-antitrypsins (alpha 1 AT's) are being isolated from plasma using gel exclusion chromatography, Concanavalin A affinity chromatography, and DEAE ion exchange chromatography. Isolated preparations of alpha 1 AT, trace-labeled with radioiodine, are being used to obtain data on the turnover of alpha 1 AT in normal subjects, patients with alpha 1 AT deficiency and their relatives and patients with chronic hepatocellular disease. The protease inhibitor genotypes of subjects donating plasma for isolation of alpha 1 AT and subjects undergoing alpha 1 AT turnover studies are determined. Alpha 1 AT's isolated from normal subjects (genotype PiMM) and from patients with alpha 1 AT deficiency (genotype PiZZ) have different degrees of sialylation. Each is labeled with a different isotope of iodine and the metabolism of the two labeled preparations are compared in the same individuals. In addition, the metabolism in vivo at alpha 1 AT which has been desialylated in vitro is being studied. This project is designed to determine whether the degree of sialylation of alpha 1 AT influences the rate at which this protein is catabolized, to evaluate the factors contributing to the low plasma concentrations of alpha 1 AT in alpha 1 AT deficiency and to assess the effect of chronic hepatocellular disease on the catabolism and/or hepatic uptake of alpha 1 AT and desialylated alpha 1 AT.